Mutations in the inosine triphosphate pyrophosphohydrolase (ITPA) gene causing enzyme deficiency were shown to have pharmacogenetic implications in azathioprine-induced adverse drug reactions. The distribution of ITPA activity as well as the types and the frequencies of gene variants associated with a lower enzyme activity were determined in healthy volunteers from a Bulgarian population. The ITPA activity was measured in 185 erythrocyte samples by an established high-performance liquid chromatography procedure. All samples were genotyped for 94C > A, IVS2 + 21A > C, and IVS2 + 68T > C/G by real-time polymerase chain reaction with hybridization probes. The ITPA activity ranged from 7.5 to 587.8 micromoL IMP/(g Hb x h) with a median value of 162.9 micromoL IMP/(g Hb x h). The enzyme activity showed significant differences between females and males (P = 0.006) with 17% higher values in men than women. Mutant allele frequencies were 0.038 (94C > A) and 0.130 (IVS2 + 21A > C). Mutations at IVS2 + 68 were not identified. Using a cutoff at 75 micromoL IMP/(g Hb x h) phenotyping detected all heterozygous carriers of 94C > A, two compound heterozygotes, all IVS2 + 21A > C homozygotes and 12.5% of IVS2 + 21A > C heterozygous cases. A novel frameshift mutation 359_366dupTCAGCACC in exon 6 was found in a subject with reduced enzyme activity of 61.2 micromoL IMP/(g Hb x h). The interindividual variability in ITPA activity among the Bulgarian population resembles the distribution of enzyme activity in other whites, although the observed median activity was approximately 25% lower in the Bulgarians [163 vs 219 micromoL IMP/(g Hb x h)]. The most common mutant allele IVS2 + 21A > C showed a similar frequency like in other white populations, whereas the 94C > A mutation was less frequently observed compared with other whites. Heterozygosity for the novel gene variant 359_366dupTCAGCACC was associated with 30% enzyme activity of the wild-type median value. The role of this rare variant for the thiopurine intolerance is not explored. These data further extend the knowledge for ITPA heterogeneity in whites.

Introduction: Diabetes mellitus (DM) is estimated to affect 2-37% of COPD patients, results varying widely between studies. DM may also correlate with quality of life and lung function. Aim: To examine correlations between DM and quality of life and lung function in COPD patients admitted to hospital with exacerbation of COPD. Patients and methods: A hundred and fifty-two patients were included in the study. They were all examined for diabetes mellitus. All patients completed CAT and mMRC questionnaires and underwent spirometry. Results: 13.2% (20/152) of patients received medications for DM. 21.7% (33/152) had newly diagnosed DM and 30.9% (47/152) had prediabetes. DM is not associated with reduced quality of life and worse pulmonary function. However, untreated DM is associated with both reduced quality of life and worse pulmonary function. HbA1c is negatively correlated with FVC and positively correlated with CAT score. Conclusions: COPD patients hospitalized for exacerbation are at high risk for impaired glucose metabolism. Untreated DM is associated with worse lung function and lower quality of life, which stresses the importance of screening for the disease. The patients may benefit from optimizing blood glucose level.

Introduction31–77% of patients with COPD have vitamin D deficiency and insufficiency, with results being highly variable between studies. Vitamin D may also correlate with disease characteristics.AimTo find out the prevalence of vitamin D deficiency and insufficiency in patients with COPD admitted for exacerbation and a risk factors for lower vitamin D levels among comorbidities and COPD characteristics.Methods152 patients were studied for vitamin D serum levels (25(OH)D). All of them were also assessed for diabetes mellitus (DM) and metabolic syndrome (MS). Data were gathered also for smoking status and exacerbations in last year. All patients completed CAT and mMRC questionnaires and underwent spirometry.ResultsA total of 83,6% of patients have reduced levels of vitamin D. 42,8% (65/152) have vitamin D insufficiency (defined as 25–50 nmol/L) and 40,8% (62/152) have vitamin D deficiency (<25 nmol/L). The mean level of 25(OH)D for all patients is 31,97 nmol/L (95%CI 29,12–34,68). Vitamin D deficiency and insufficiency are more prevalent in females vs. males (97,7 vs 77,8%; p = 0.003). The prevalence and severity of vitamin D deficiency and insufficiency in this study is significantly higher when compared to an unselected Bulgarian population (prevalence 75,8%; mean level 38,75 nmol/L). Vitamin D levels correlate with quality of life (measured by the mMRC scale) and lung function (FVC, FEV1, FEV6, FEF2575, FEV3, but not with FEV1/FVC ratio and PEF), it does not correlate with the presence of arterial hypertension, DM, MS and number of moderate, severe and total exacerbations. Vitamin D deficiency is a risk factor for longer hospital stay.ConclusionsThe patients with COPD admitted for exacerbation are a risk group for vitamin D deficiency and insufficiency, which is associated with worse disease characteristics.

No abstract

The metabolic syndrome (MS) affects 21-53% of patients with chronic obstructive pulmonary disease (COPD) with a higher prevalence in the early stages of COPD, with results being highly variable between studies. MS may also correlate with disease characteristics. The aim of the study is to examine the prevalence of MS and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. 152 patients with COPD admitted for exacerbation were studied for presence of MS. All of them were also assessed for vitamin D status and diabetes mellitus type 2 (DM). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. 25% of patients have MS. 23,1% of the male and 29,5% of the female patients have MS (p>0.05). The prevalence of MS in this study is significantly lower when compared to a national representative study (44,6% in subjects over 45 years). 69,1% of all patients and 97,4% from MS patients have arterial hypertension. The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p=0.002 and p=0.001 respectively) and higher total CAT score (p=0.017). Average BMI is 27,31. None of the patients have MS and BMI <25. There is a correlation between the presence of MS and DM (p=0.008) and with the number of exacerbations in the last year (p=0.015). There is no correlation between the presence of MS and the pulmonary function. This study among hospitalized COPD patients finds comparable but relatively low prevalence of MS (25%) compared to previously published data (21-53%) and lower prevalence compared to general population (44,6%). MS may impact natural course and the number of exacerbations of COPD. Having in mind that MS is more common in the early stages and decreases with COPD progression, the COPD patients admitted for exacerbation may be considered as having advanced COPD.